Two Different Immune Profiles Are Identified in Sentinel Lymph Nodes of Early-Stage Breast Cancer

Author:

Ribeiro Joana Martins1ORCID,Mendes João12ORCID,Gante Inês34ORCID,Figueiredo-Dias Margarida34ORCID,Almeida Vânia56,Gomes Ana5ORCID,Regateiro Fernando Jesus1,Regateiro Frederico Soares278ORCID,Caramelo Francisco2910ORCID,Silva Henriqueta Coimbra1210ORCID

Affiliation:

1. Laboratory of Sequencing and Functional Genomics of UCGenomics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

2. Institute for Clinical and Biomedical Research (iCBR), Centre of Investigation on Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

3. Gynecology Department, Coimbra Hospital and University Center, Unidade Local de Saúde de Coimbra, 3004-561 Coimbra, Portugal

4. Gynecology University Clinic, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

5. Department of Pathology, Coimbra Hospital and University Center, Unidade Local de Saúde de Coimbra, 3004-561 Coimbra, Portugal

6. Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

7. Allergy and Clinical Immunology Unit, Coimbra Hospital and University Center, Unidade Local de Saúde de Coimbra, 3004-561 Coimbra, Portugal

8. Institute of Immunology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

9. Laboratory of Biostatistics and Medical Informatics (LBIM), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

10. Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-504 Coimbra, Portugal

Abstract

In the management of early-stage breast cancer (BC), lymph nodes (LNs) are typically characterised using the One-Step Nucleic Acid Amplification (OSNA) assay, a standard procedure for assessing subclinical metastasis in sentinel LNs (SLNs). The pivotal role of LNs in coordinating the immune response against BC is often overlooked. Our aim was to improve prognostic information provided by the OSNA assay and explore immune-related gene signatures in SLNs. The expression of an immune gene panel was analysed in SLNs from 32 patients with Luminal A early-stage BC (cT1-T2 N0). Using an unsupervised approach based on these expression values, this study identified two clusters, regardless of the SLN invasion: one evidencing an adaptive anti-tumoral immune response, characterised by an increase in naive B cells, follicular T helper cells, and activated NK cells; and another with a more undifferentiated response, with an increase in the activated-to-resting dendritic cells (DCs) ratio. Through a protein—protein interaction (PPI) network, we identified seven immunoregulatory hub genes: CD80, CD40, TNF, FCGR3A, CD163, FCGR3B, and CCR2. This study shows that, in Luminal A early-stage BC, SLNs gene expression studies enable the identification of distinct immune profiles that may influence prognosis stratification and highlight key genes that could serve as potential targets for immunotherapy.

Funder

GenomePT—National Laboratory for Genome Sequencing and Analysis

Central Region Training Project for Personalized/Precision Medicine, with a genomic basis

programme CENTRO2020

Publisher

MDPI AG

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